Role of blood- and tissue-associated inducible nitric-oxide synthase in colonic inflammation |
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| Authors: | Krieglstein Christian F Anthoni Christoph Cerwinka Wolfgang H Stokes Karen Y Russell Janice Grisham Matthew B Granger D Neil |
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| Affiliation: | Department of General Surgery, Westfalian Wilhelm's University, Muenster, Germany. |
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| Abstract: | There is evidence that inducible nitric-oxide synthase (iNOS)-derived NO contributes to the pathophysiology of intestinal inflammation. The aims of this study were to assess the role of iNOS in the development of dextran sodium sulfate (DSS)-induced colonic inflammation and to define the contribution of tissue-specific iNOS expression to this inflammatory response. Study groups included: 1) wild-type (WT) mice; 2) WT=>WT bone marrow chimeras with normal iNOS function; 3) WT=>iNOS-/- chimeras (with functional blood cell iNOS, but iNOS-deficient tissue); 4) iNOS-/-=>WT chimeras (with iNOS-deficient blood cells, but normal tissue iNOS activity); and 5) iNOS-deficient mice. In WT mice and WT=>WT chimeras, DSS-induced colonic inflammation was characterized by bloody diarrhea and a high disease activity index. However, WT=>iNOS-/- and iNOS-/-=>WT chimeras and iNOS-/- mice exhibited an attenuated disease activity index, with parallel changes in histopathology. Colonic myeloperoxidase (MPO) was comparably elevated in DSS-treated WT mice (30.1+/-1.7) and WT=>WT chimeras (29.0+/-1), whereas MPO was significantly reduced in iNOS-/- mice and iNOS-/-=>WT chimeras (9.5+/-1.7 and 15.6+/-2.2, respectively). WT=>iNOS-/- chimeras exhibited the lowest MPO activity (3.7+/-0.6). Our findings implicate both blood cell- and tissue-derived iNOS in DSS-induced colonic inflammation, with tissue-associated iNOS making a larger contribution to the recruitment of inflammatory cells. |
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